Letter pubs.acs.org/OrgLett
Synthesis of Trifluoromethyl-allenes by Gold-Catalyzed Rearrangement of Propargyl Benzyl Ethers Arnaud Boreux,†,‡,∥ Geoffroy H. Lonca,†,∥ Olivier Riant,*,‡ and Fabien Gagosz*,†,§ †
Laboratoire de Synthèse Organique, UMR 7652 CNRS/Ecole Polytechnique, Ecole Polytechnique, Route de Saclay, 91128 Palaiseau, France ‡ Institute of Condensed Matter and Nanosciences (IMCN), Division of Molecules, Solids and Reactivity (MOST), Université Catholique de Louvain, Place Louis Pasteur 1, bte L4.01.02, 1348 Louvain-la-Neuve, Belgium S Supporting Information *
ABSTRACT: A new method for the synthesis of trifluoromethyl-allenes from easily accessible α-trifluoromethyl-propargyl benzyl ether derivatives following a gold-catalyzed intramolecular hydride transfer has been developed. Various di- and trisubstituted trifluoromethyl-allenes were obtained in good to excellent yields.
Scheme 1. Synthetic Approaches to Trifluoromethyl-allenes
CF3-containing building blocks are privileged structural motifs in medicinal chemistry and agrochemistry.1 As a consequence, substantial efforts have been made over the years by synthetic organic chemists in order to design and develop methods allowing efficient access to a variety of trifluoromethylated species.2 Given the unique reactivity of allenes3 and their ability to react in a wide range of transformations to build up valuable complex structures,4 special attention has naturally been brought to trifluoromethyl-allenes and how to access them. The first syntheses of CF3-allenes, which were reported several decades ago,5 generally suffer from low efficiency and exhibit limited scope. Current efforts in the domain are focused on addressing these issues. From a general point of view, currently available synthetic routes to CF3-allenes 1 can be classified into two main categories A and B (Scheme 1, top). CF3-allenes can be prepared starting from alkynyl or alkenyl substrates already possessing a CF3 moiety (category A) by elimination reactions,6 isomerizations,7 sigmatropic rearrangements,8 SN2′ reactions,9 and metal-catalyzed processes.10,11 A more recently developed alternative access to CF3-allenes relies on the use of a “Cu-CF3” reagent to introduce the CF3 moiety on an activated alkynyl substrate (category B).12 Even if these different methods are complementary with each other and allow an overall access to a variety of functionalized CF3allenes, they are still suffering some limitations mainly in terms of product formation selectivity and substrate accessibility. Taking into account that alkyne derivatives are privileged substrates for the synthesis of CF3-allenes 1 (Scheme 1, top) and considering the remarkable ability of gold catalysts to convert alkynes into a range of valuable structural motifs,13 we envisaged gold catalysis as a potential useful synthetic tool for the rapid, efficient, and selective synthesis of a range of diversely substituted CF3-allenes.14 © 2016 American Chemical Society
Our strategy, which is presented in the bottom part of Scheme 1, relies on previous findings by us and others that gold catalysts could be used to convert propargyl benzyl ethers into Received: September 1, 2016 Published: September 26, 2016 5162
DOI: 10.1021/acs.orglett.6b02636 Org. Lett. 2016, 18, 5162−5165
Letter
Organic Letters allenes.15,16 We indeed conceived that an activation of alkyne substrate 2 by an electrophilic gold species might induce a 1,5hydride shift that would lead to the formation of an oxocarbenium intermediate 3. A subsequent elimination of benzaldehyde with concomitant regeneration of the gold catalyst would deliver CF3-allene 4. This approach, which could lead to the formation of up to trisubstituted CF3-allenes, appeared to be particularly appealing since the required trifluoromethylated substrates 2 could be rapidly and conveniently obtained in a three-step sequence starting from the readily available and relatively cheap ethyl trifluoroacetate. We started our investigations with model substrate 2a and looked for catalytic conditions that could allow its conversion into CF3-allene 4a. The main results are compiled into Table 1.
Scheme 2. Substrate Scope: Gold-Catalyzed Formation of Trifluoromethyl-allenes,
Table 1. Optimization of the Catalytic System
a
4a is a volatile compound. The yield was assessed by 1H NMR spectroscopy using 1,2-dichloroethane as an internal standard. bCDCl3 was dried over 4 Å MS prior to usage.
The activity of 5, a gold catalyst which proved its efficiency in hydride transfer reactions,15,17 was first evaluated. Substrate 2a was treated with 4 mol % of 5 in refluxing CDCl3,18and the reaction was monitored by 1H NMR spectroscopy (Table 1, entry 1). The formation of CF3-allene 4a could be observed, thus validating our approach, but the conversion of 2a was very poor (
